Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/12640 |
Resumo: | Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil |
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Fonseca, Nayara CristinaCruz, Luana Faria daVillela, Filipe da SilvaPereira, Glaécia Aparecida do NascimentoSiqueira Neto, Jair Lage deKellar, DanielleSuzuki, Brian M.Ray, DebalinaSouza, Thiago Belarmino deAlves, Ricardo JoséSales Júnior, Policarpo AdemarRomanha, Alvaro JoséMurta, Silvane Maria FonsecaMcKerrow, James H.Caffrey, Conor R.Oliveira, Renata Barbosa deFerreira, Rafaela Salgado2016-01-28T12:38:57Z2016-01-28T12:38:57Z2015FONSECA, Nayara Cristina et al. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother., Vol. 59n. 5, p. 2666–2677, 2015.0066-4804https://www.arca.fiocruz.br/handle/icict/1264010.1128/AAC.04601-14engAmerican Society for MicrobiologySynthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil/Ministerio da Educação. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Brasília, DF, BrasilUniversity of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. San Diego, CA, USAUniversity of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USAUniversity of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USAUniversity of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USAUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil/Universidade Federal de Santa Catarina. Departamento de Microbiologia, Imunologia e Parasitologia. Florianópolis, SC, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilUniversity of California. Skaggs School of Pharmacy and Pharmaceutical Sciences. San Diego, CA, USAUniversity of California. Center for Discovery and Innovation in Parasitic Diseases and Department of Pathology. San Francisco, CA, USAUniversidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilThe pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series.Cathepsin B/metabolismCysteine ProteinaseInhibitors/chemical synthesisCysteine ProteinaseInhibitors/pharmacologyTrypanocidal Agents/chemical synthesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12640/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSynthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity.pdfSynthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity.pdfapplication/pdf4194394https://www.arca.fiocruz.br/bitstream/icict/12640/2/Synthesis%20of%20a%20Sugar-Based%20Thiosemicarbazone%20Series%20and%20Structure-Activity.pdfeac1a47b149b813e4fa83f370992048cMD52TEXTSynthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity.pdf.txtSynthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity.pdf.txtExtracted texttext/plain14https://www.arca.fiocruz.br/bitstream/icict/12640/3/Synthesis%20of%20a%20Sugar-Based%20Thiosemicarbazone%20Series%20and%20Structure-Activity.pdf.txt77cf8f2991edfd65482448bab578abe7MD53icict/126402019-06-19 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| dc.title.pt_BR.fl_str_mv |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| title |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| spellingShingle |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 Fonseca, Nayara Cristina Cathepsin B/metabolism Cysteine Proteinase Inhibitors/chemical synthesis Cysteine Proteinase Inhibitors/pharmacology Trypanocidal Agents/chemical synthesis |
| title_short |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| title_full |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| title_fullStr |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| title_full_unstemmed |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| title_sort |
Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1 |
| author |
Fonseca, Nayara Cristina |
| author_facet |
Fonseca, Nayara Cristina Cruz, Luana Faria da Villela, Filipe da Silva Pereira, Glaécia Aparecida do Nascimento Siqueira Neto, Jair Lage de Kellar, Danielle Suzuki, Brian M. Ray, Debalina Souza, Thiago Belarmino de Alves, Ricardo José Sales Júnior, Policarpo Ademar Romanha, Alvaro José Murta, Silvane Maria Fonseca McKerrow, James H. Caffrey, Conor R. Oliveira, Renata Barbosa de Ferreira, Rafaela Salgado |
| author_role |
author |
| author2 |
Cruz, Luana Faria da Villela, Filipe da Silva Pereira, Glaécia Aparecida do Nascimento Siqueira Neto, Jair Lage de Kellar, Danielle Suzuki, Brian M. Ray, Debalina Souza, Thiago Belarmino de Alves, Ricardo José Sales Júnior, Policarpo Ademar Romanha, Alvaro José Murta, Silvane Maria Fonseca McKerrow, James H. Caffrey, Conor R. Oliveira, Renata Barbosa de Ferreira, Rafaela Salgado |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Fonseca, Nayara Cristina Cruz, Luana Faria da Villela, Filipe da Silva Pereira, Glaécia Aparecida do Nascimento Siqueira Neto, Jair Lage de Kellar, Danielle Suzuki, Brian M. Ray, Debalina Souza, Thiago Belarmino de Alves, Ricardo José Sales Júnior, Policarpo Ademar Romanha, Alvaro José Murta, Silvane Maria Fonseca McKerrow, James H. Caffrey, Conor R. Oliveira, Renata Barbosa de Ferreira, Rafaela Salgado |
| dc.subject.en.pt_BR.fl_str_mv |
Cathepsin B/metabolism Cysteine Proteinase Inhibitors/chemical synthesis Cysteine Proteinase Inhibitors/pharmacology Trypanocidal Agents/chemical synthesis |
| topic |
Cathepsin B/metabolism Cysteine Proteinase Inhibitors/chemical synthesis Cysteine Proteinase Inhibitors/pharmacology Trypanocidal Agents/chemical synthesis |
| description |
Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Produtos Farmacêuticos. Belo Horizonte, MG, Brasil |
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2015 |
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2015 |
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2016-01-28T12:38:57Z |
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2016-01-28T12:38:57Z |
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info:eu-repo/semantics/article |
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FONSECA, Nayara Cristina et al. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother., Vol. 59n. 5, p. 2666–2677, 2015. |
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https://www.arca.fiocruz.br/handle/icict/12640 |
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0066-4804 |
| dc.identifier.doi.none.fl_str_mv |
10.1128/AAC.04601-14 |
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FONSECA, Nayara Cristina et al. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases: rhodesain; cruzain and Schistosoma mansoni cathepsin B1. Antimicrob Agents Chemother., Vol. 59n. 5, p. 2666–2677, 2015. 0066-4804 10.1128/AAC.04601-14 |
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American Society for Microbiology |
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American Society for Microbiology |
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